The overall goal of this project is to demonstrate the feasibility of using ultrasound to temporarily make vascular tissue more permeable and thereby deliver drug to the cells in the vessel wall (e.g. smooth muscle cells). EKOS has developed an ultrasound-catheter device for the transmural delivery of drugs and we are seeking to understand the mechanisms by which ultrasound can make tissue more permeable and thereby enhance transport of drugs and genes into target tissues and inside of cells. We propose the use of ultrasound to transiently disrupt cell membranes for delivery of drugs, proteins, and DNA. This non-chemical, non-viral, and minimally-invasive approach could provide a safe means for targeted cell uptake in the treatment of restenosis and other cardiovascular diseases. Despite compelling initial experiments, ultrasound-mediated cell permeabilization has been insufficiently characterized to rationally design protocols for applications. understanding the effects of ultrasound parameters on cells and reproducibly achieving those effects at different times and in different patients is essential to developing a clinical product. The specific aims are: 1. Determine the effect of acoustic parameters on molecular uptake and cell viability 2. Characterize the size and lifetime of membrane disruptions 3. Identify acoustic signals that correlate with membrane disruption threshold PROPOSED COMMERCIAL APPLICATION: Our product will be an ultrasound catheter device that actively delivers drug into the artery wall for the treatment of restenosis.